Diabetic nephropathy (DN) is the leading cause of end-stage renal disease in diabetics worldwide, yet most patients with type-2 diabetes mellitus are not formally evaluated with a renal biopsy. The diagnosis is almost always based on clinical grounds. A wide spectrum of non-diabetic renal disease (NDRD) is reported to occur in patients with type-2 diabetes. It has been estimated that up to one-third of all diabetic patients who present with proteinuria are suffering from NDRD. The aim of this analysis was to evaluate the prevalence and etiology of NDRD in patients with type-2 diabetes. We retrospectively reviewed the medical records of patients with type-2 diabetes who underwent kidney biopsy on clinical suspicion of NDRD (absence of diabetic retinopathy and/or neuropathy; short duration of diabetes, i.e. less than five years) from January 2003 through December 2007 at the Aga Khan University Hospital, Karachi. Based on the biopsy findings, patients were grouped as Group-I, isolated NDRD; Group-II, NDRD with underlying DN; and Group-III, isolated DN. Of 68 patients studied, 75% were males and the mean age was 56 years. The mean duration of diabetes was nine years. Group-I included 34 patients (52%), Group-II included 11 patients (17%) and Group-III included 23 patients (31%). Among the Group-I patients, the mean age was 56 years (41-77 years). The most common NDRDs were acute interstitial nephritis (32%), diffuse proliferative glomerulonephritis (17%); membranous nephropathy (12%) and crescentic glomerulonephritis (12%). Among Group-II, the mean age was 60 years (46-71 years), and the most common lesion was interstitial nephritis superimposed on underlying DN (63% cases). Among Group-III, the mean age was 53 years (42- 80 years). The mean proteinuria was 5, 6.3 and 7.3 g/24 h of urine collection in Groups I, II and III, respectively (P = NS). The mean duration of diabetes was 7.3, 11.7 and 10.7 years in Groups I, II and III, respectively. The duration of diabetes was significantly less in Group-I compared with Group-II and Group-III (P = 0.04). Our study suggests that the prevalence of NDRD (either isolated or superimposed on underlying DN) is high in appropriate clinical settings. Performing renal biopsy in diabetics with no extrarenal end organ damage other than nephropathy helps to diagnose and treat NDRD. This is the first report from Pakistan documenting the prevalence of NDRD in patients with type-2 diabetes.